Neuroleptic drugs dyskinesia

Figure 7.8 Dopamine and motor function. When nigrostriatal dopamine activity is normal so is motor function. Any reduction in this DA activity, as in Parkinson s disease, results in reduced motor activity, i.e. akinesia. By contrast, too much DA activity, as in Huntington s Chorea, produces abnormal motor function, i.e. dyskinesia. The latter may be controlled by neuroleptic drugs (DA antagonists) but they can swing the balance in DA activity sufficiently to produce akinesia (Parkinsonism). DA agonists (and levodopa) may overcome akinesia but can induce DA overactivity and dyskinesia (peak dose effect) (see Chapter 15)...

In addition, there is evidence that the neuroleptic drugs produce neurological and psychiatric disturbance in their own right. The abnormal movements associated with tardive dyskinesia, a condition they are... 

Correct choice = D. Tardive dyskinesia appears to be produced to the same degree and frequency by all the neuroleptic drugs when used in equieffective antipsychotic doses. 

More than a dozen drugs, almost all of them in use for many years, can be classified as neuroleptics. The phenothiazine derivatives were originally the most commonly used class of neuroleptic drugs. Chlorproma-zine is the prototype, developed in France and introduced into North America in 1953 by Heinz Lehmann. Its brand name in Canada and England is Largactil, and in the United tates, Thorazine. The antidepressant amoxapine (Asendin) is metabolized into a neuroleptic and has similar effects and, more important, adverse effects, such as tardive dyskinesia. All the classic neuroleptics block dopamine, but all of them also affect other neurotransmitter systems. 

I put my patients on neuroleptic drugs because they re psychotic. Now you re saying that the same drug that controls their schizophrenia also causes a psychosis and that on top of that the drug causes tardive dyskinesia one third of the time. It s a Hobson s choice. My patients are going to lose in the end either way. 

Extrapyramidal symptoms (including akathisia, dystonia, dyskinesia, tardive dyskinesia, parkinsonism, and brux-ism) have been reported in association with SSRIs, especially in the presence of predisposing factors (SEDA-14, 14 12). Current data suggest that SSRIs should be used with caution in patients with parkinsonism (see the monograph on fluoxetine). Concomitant treatment with neuroleptic drugs and high concentrations of SSRIs seems to predispose to extrapyramidal symptoms. Elderly patients and women are also at increased risk. 

Neuroleptic drugs can produce a variety of adverse effects in several organ systems. Extrapyramidal reactions and sedation are common less common are seizures, unwanted behavioral effects, and tardive dyskinesia. Most neuroleptic drugs have anticholinergic effects and commonly produce dry mouth, blurred vision, and constipation. Postural hypotension is common. These effects usually disappear when the drug is stopped or the dosage is reduced. 

Gag and cough reflexes can be suppressed by neuroleptic drugs (SED-11, 107). Periodic examination of the gag reflex, particularly in patients with tardive dyskinesia, has been recommended. 

The CYP2D6 genotype is not a determinant of susceptibility to acute dystonic reactions, but may be a contributory factor in neuroleptic drug-induced movement disorders, including tardive dyskinesia (176). 

A therapeutic role for nefazodone 100 mg bd has been suggested in the treatment of neuroleptic drug-induced extrapyramidal signs, based on the results of a placebo-controlled, randomized study in 49 patients (197). There were no differences in akathisia or tardive dyskinesia between the two groups. However it should be noted that nefazodone has been withdrawn in most countries owing to the risk of severe liver damage. 

Whether certain typical neuroleptic drugs are more likely than others to cause tardive dyskinesia is unknown (245), but virtually all typical neuroleptic drugs have been associated with it (255). Although there is evidence that atypical neuroleptic drugs are associated with a low risk (256,257), this needs to be evaluated in more prospective studies (256,258). 

Discussion about tardive dyskinesia is necessary in the process of obtaining informed consent to treatment with neuroleptic drugs (SEDA-15, 46 SEDA-21, 42 SEDA-21, 45). The effect of education about tardive dyskinesia has been evaluated in 56 patients taking maintenance neuroleptic drugs, who completed a questionnaire assessing their knowledge of the condition (262). Education made patients more knowledgeable at 6 months, but had no effect on the clinical outcome. 

Tardive dyskinesia usually occurs after long-term use of neuroleptic drugs, but some cases of early onset (less than 1 year) have been reported (SEDA-6, 47 SEDA-7, 61). The incidence among patients with extrapyramidal effects... 

Although there are difficulties in establishing a reference figure for the incidence or prevalence of dyskinesia, Australian psychiatrists seem to underestimate the prevalence of tardive dyskinesia. According to a survey of 139 psychiatrists, 80% estimated the prevalence of mild reversible tardive dyskinesia as being 5% of those treated with neuroleptic drugs (277). 

Chronically hospitalized elderly inpatients with schizophrenia (n = 121 mean age 74 years) were rated for tardive dyskinesia and cognition (288). Subjects with tardive dyskinesia (60%) were older than those without. In subjects who were taking typical neuroleptic drugs (n = 119) there was no difference in dosage between those with and without tardive dyskinesia. Cognitive scores (Mini-Mental Status Examination) were significantly lower in the subjects with tardive dyskinesia... 

Conversely, tardive dyskinesia is said to be less common in young than in old patients, and a lower incidence has been observed in a retrospective chart review in 40 adolescents taking neuroleptic drugs (289). After 2 years, the figure was 18% although comparability of those studies is far from optimal. Average daily dose, non-adherence to therapy, early age of illness, and concomitant use of antiparkinsonian drugs were associated with increased susceptibility. 

Of 34 schizophrenic children and adolescents followed after a drug-free period that lasted up to 4 weeks at 2-year intervals, 17 had either withdrawal dyskinesia or tardive dyskinesia at some time. Patients who developed dyskinesia had greater premorbid impairment and a greater severity of positive symptoms at baseline, and there was a trend toward more months of neuroleptic drug exposure. 

In a retrospective study in a psychiatric hospital in Curasao, Netherlands Antilles, 133 Afro-Caribbean inpatients (mean age 52 years), with no organic disorders and a history of current use of neuroleptic drugs for at least 3 months, were assessed for tardive dyskinesia (291). The prevalence was 36%. When the number of interruptions to neuroleptic drug therapy was split into up to two and more than two, the resulting adjusted odds ratio was 3.29 (95% Cl = 1.27, 8.49). Thus, the number of interruptions turned out to be the second risk factor after age. Cumulative dosages of neuroleptic or anticholinergic drugs were not risk factors. 

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